Rheumatoid arthritis (RA) affects 1% of the adults worldwide. RA's hallmark is leukocyte infiltration of the synovium. This process stimulates the proliferation of apoptosis-resistant fibroblast-like synoviocytes (FLS), leading to pannus formation and joint destruction. Intra-articular expression of cytokines, particularly that of TNF-α and IL-1β, plays key roles in RA pathogenesis.
Osteoarthritis (OA), a slowly progressing disease resulting in articular cartilage fibrillation and loss, is the most common form of arthritis (Hunter, 2009. Risk stratification for knee osteoarthritis progression: a narrative review. Osteoarthritis Cartilage May 3, 2009). Approximately 10-50% of the elderly population is affected by OA, a quarter of whom are severely disabled due to joint symptoms (Haywood et al., 2003. Inflammation and angiogenesis in osteoarthritis. Arthritis Rheum 48:2173-7). The degradative process is believed to be largely mediated by proteases belonging to the matrix metalloproteinase (MMP) class of enzymes. Among these, MMP-1 and MMP-13 are considered to be of particular interest since they directly degrade the components of the cartilage matrix including aggrecan and collagen. Cytokines such as interleukin-1β (IL-1β), are known to strongly induce the production of MMP-1 and MMP-13 by articular joint cells. IL-1β and TNF-α, are widely assumed to play a major role in the pathological process of cartilage degeneration. Previously, a newly designed surgical patella strengthening (SPS)-induced model of OA in BALB/c mice had been setup and OA markers had been established by investigating the relationship between synovial and MMPs (Chia et al., Experimental osteoarthritis induced by surgical realignment of the patella in BALB/c mice. J Bone Joint Surg Br. 2010 December; 92(12):1710-6).
Antrodia cinnamomea CHANG TT & WN CHOU (Chinese name, niu-chang-chih or niu-chang-ku; synonym Antrodia camphorata WU SH et al.) is a new species of the genus Antrodia (family polyporaceae, Aphyllophorales) that is parasitic on the inner cavity of the endemic species Cinnamomum kanehirai HAY. This endangered species has been used in Taiwan to treat food, alcohol, and drug intoxication, diarrhea, abdominal pain, hypertension, skin itching and liver cancer as a Chinese folk medicine. The hot water extract of A. cinnamomea has hepatoprotective effect. Han et al. showed that the hepatoprotective activity of the extract in mice with Propionibacterium acnes (P. acnes)—lipopolysaccharide (LPS) induced hepatotoxicity (Han et al., Protective effects of a neutral polysaccharide isolated from the mycelium of Antrodia cinnamomea on Propionibacterium acnes and lipopolysaccharide induced hepatic injury in mice. Chem Pharm Bull (Tokyo). 2006 April; 54(4):496-500).
Anti-type II collagen antibody (anti-CII Ab) is an autoantibody known to be present in RA patients (Firestein, Evolving concepts of rheumatoid arthritis. Nature 2003; 423:356-61). CAIA (collagen antibody-induced arthritis) is commonly used as an RA model for screening antirheumatic drugs because of its similarity with human RA. In the CAIA model, anti-CII Ab plays an important role; it induces arthritis in mice by passive transfer. An arthritis model using a mixture of 4 monoclonal anti-CII Abs has been established. This model can be prepared in constant yields by using various strains of mice, independent of MHC haplotypes. The data presented previously showed that IL-1beta concentration in irrigation fluid and relative expression level of IL-1beta mRNA in the synovium have potential as therapeutic markers in studying and treating CAIA (Chia et al., IL-1beta in irrigation fluid and mRNA expression in synovial tissue of the knee joint as therapeutic markers of inflammation in collagen antibody-induced arthritis. Dis Markers. 2009; 26(1):1-7). The previous study also showed that the matrix metalloproteinase (MMP)-9 (gelatinase B) mRNA level is a suitable marker for both acute and chronic stage, whereas IL-1beta is a marker only for the acute stage of the CAIA murine model (Chia et al., MMP-9 mRNA as a therapeutic marker in acute and chronic stages of arthritis induced by type II collagen antibody. J Formos Med Assoc. 2008 March; 107(3):245-52).
U.S. Pat. No. 7,109,232 discloses compounds and extracts from mycelium of Antrodia cinnamomea and the composition comprising the compound, which has anti-inflammation activity. But in its experiment, the inflammation model is induced by carrageenan, and only hind paw edema of rats are measured. The amelioration of systemic disease activity and the mechanism are still unknown.
U.S. Pat. No. 7,732,482 discloses a method of treating fibrosis in a mammal by the compounds from mycelium of Antrodia cinnamomea, wherein the fibrosis is mediated by TGF-β, and the TGF-β is associated with a disease state such as rheumatoid arthritis. But fibrosis can not be directly linked to rheumatoid arthritis since rheumatoid arthritis does not necessarily result in fibrosis. In addition, the mechanism of anti-disease activity of the compounds in rheumatoid arthritis is not disclosed.